A study protocol to characterise pathophysiological and molecular markers of rheumatic heart disease and degenerative aortic stenosis using multiparametric cardiovascular imaging and multiomics techniques.

INTRODUCTION: Rheumatic heart disease (RHD), degenerative aortic stenosis (AS), and congenital valve diseases are prevalent in sub-Saharan Africa. Many knowledge gaps remain in understanding disease mechanisms, stratifying phenotypes, and prognostication. Therefore, we aimed to characterise patients through clinical profiling, imaging, histology, and molecular biomarkers to improve our understanding of the pathophysiology, diagnosis, and prognosis of RHD and AS. METHODS: In this cross-sectional, case-controlled study, we plan to recruit RHD and AS patients and compare them to matched controls. Living participants will undergo clinical assessment, echocardiography, CMR and blood sampling for circulatory biomarker analyses. Tissue samples will be obtained from patients undergoing valve replacement, while healthy tissues will be obtained from cadavers. Immunohistology, proteomics, metabolomics, and transcriptome analyses will be used to analyse circulatory- and tissue-specific biomarkers. Univariate and multivariate statistical analyses will be used for hypothesis testing and identification of important biomarkers. In summary, this study aims to delineate the pathophysiology of RHD and degenerative AS using multiparametric CMR imaging. In addition to discover novel biomarkers and explore the pathomechanisms associated with RHD and AS through high-throughput profiling of the tissue and blood proteome and metabolome and provide a proof of concept of the suitability of using cadaveric tissues as controls for cardiovascular disease studies.

Greater Disease Severity and Worse Clinical Outcomes in Patients Hospitalised with COVID-19 in Africa.

Background: COVID-19 cardiovascular research from Africa is limited. This study describes cardiovascular risk factors, manifestations, and outcomes of patients hospitalised with COVID-19 in the African region, with an overarching goal to investigate whether important differences exist between African and other populations, which may inform health policies. Methods: A multinational prospective cohort study was conducted on adults hospitalised with confirmed COVID-19, consecutively admitted to 40 hospitals across 23 countries, 6 of which were African countries. Of the 5,313 participants enrolled globally, 948 were from African sites (n = 9). Data on demographics, pre-existing conditions, clinical outcomes in hospital (major adverse cardiovascular events (MACE), renal failure, neurological events, pulmonary outcomes, and death), 30-day vitality status and re-hospitalization were assessed, comparing African to non-African participants. Results: Access to specialist care at African sites was significantly lower than the global average (71% vs. 95%), as were ICU admissions (19.4% vs. 34.0%) and COVID-19 vaccination rates (0.6% vs. 7.4%). The African cohort was slightly younger than the non-African cohort (55.0 vs. 57.5 years), with higher rates of hypertension (48.8% vs. 46.9%), HIV (5.9% vs. 0.3%), and Tuberculosis (3.6% vs. 0.3%). In African sites, a higher proportion of patients suffered cardiac arrest (7.5% vs. 5.1%) and acute kidney injury (12.7% vs. 7.2%), with acute kidney injury (AKI) appearing to be one of the strongest predictors of MACE and death in African populations compared to other populations. The overall mortality rate was significantly higher among African participants (18.2% vs. 14.2%). Conclusions: Overall, hospitalised African patients with COVID-19 had a higher mortality despite a lower mean age, contradicting literature that had previously reported a lower mortality attributed to COVID-19 in Africa. African sites had lower COVID-19 vaccination rates and higher AKI rates, which were positively associated with increased mortality. In conclusion, African patients were hospitalized with more severe COVID-19 cases and had poorer outcomes.

Chronic rheumatic heart disease with recrudescence of acute rheumatic fever on histology: a case report.

Background: Rheumatic heart disease (RHD) is endemic in sub-Saharan Africa where it is the leading cause of cardiovascular mortality in the young. Rheumatic heart disease results from recurrent episodes of acute rheumatic fever (ARF), which are often difficult to diagnose clinically. Acute rheumatic fever may be diagnosed based on the revised Jones Criteria 2015 for the diagnosis of ARF. Histologically, acute rheumatic valvulitis manifests with active inflammation characterized by lymphocytic infiltration, Aschoff bodies, and Anitschkow cells. Chronic rheumatic valvulitis is associated with neovascularization, and/or dystrophic calcification. The combination of histological features of both ARF and chronic RHD is a rare finding. Case summary: Here we report on a case of a 59-year-old woman with mixed aortic and mitral valve disease of probable rheumatic aetiology (elevated C-reactive protein and prolonged PR interval) and with histological evidence of lymphocytic infiltration, Aschoff bodies, and fibrinoid necrosis admixed with features of chronic RHD. Discussion: Cases of chronic RHD admixed with ARF are very rare; however, they should be considered in regions with a high prevalence of RHDs.

T cell responses to SARS-CoV-2 spike cross-recognize Omicron.

The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations1,2 that contribute to viral escape from antibody neutralization3-6 and reduce vaccine protection from infection7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients (n = 70). Between 70% and 80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere9-12.

Cardiovascular imaging modalities in the diagnosis and management of rheumatic heart disease.

Rheumatic heart disease (RHD) is prevalent in sub-Saharan Africa, where the capacity for diagnosis and evaluation of disease severity and complications is not always optimal. While the medical history and physical examination are important in the assessment of patients suspected to have RHD, cardiovascular imaging techniques are useful for confirmation of the diagnosis. Echocardiography is the workhorse modality for initial evaluation and diagnosis of RHD. Cardiovascular magnetic resonance is complementary and may provide additive information, including tissue characteristics, where echocardiography is inadequate or non-diagnostic. There is emerging evidence on the role of computed tomography, particularly following valve replacement surgery, in the monitoring and management of RHD. This article summarises the techniques used in imaging RHD patients, considers the evidence base for their utility, discusses their limitations and recognises the clinical contexts in which indications and imaging with various modalities are expanding.

Interplay of COVID-19 and cardiovascular diseases in Africa: an observational snapshot.

The COVID-19 pandemic, which started around December 2019 has, at present, resulted in over 450,000 deaths globally, and approximately 1% of these deaths have been reported in Africa. Despite the high prevalence of COVID-19 risk factors, namely: hypertension, diabetes, chronic pulmonary disease, cardiovascular diseases (CVDs) such as rheumatic heart disease, compromised immunity and obesity, low case fatality rates have been recorded in many parts of Africa so far. COVID-19 severity has previously been shown to be worse in patients with CVD and hypertension. We observed the severity of COVID-19 and mortality rates in Africa, and compared outcomes with prevalence of established risk factors (hypertension and CVD). We stratified data as per the United Nations' 5 African subregions. North African countries show a positive association between the risk factors and the mortality rates from COVID-19. However, we observed discordant patterns in the relationship between COVID-19, and either CVD or hypertension, in sub-Saharan African countries. In this paper, we also review the pathogenesis of SARS-CoV-2 infection and how it worsens CVD and postulate that the differences in modulation of the renin-angiotensin-aldosterone system (RAAS) axis which controls angiotensin-converting enzyme (ACE)/ACE2 balance may be an important determinant of COVID-19 outcomes in Africa.

Rheumatic fever and rheumatic heart disease: Facts and research progress in Africa.

In recent years, the devastating effect of rheumatic fever (RF) and rheumatic heart disease (RHD) in Africa has been acknowledged by Institutions such as the Pan-African Society of Cardiology, the African Union Commission, and the World Health Organization. Key priorities set to eradicate RF and RHD include diagnosing and managing RF and RHD, building registries, improving adequate supplies of benzathine penicillin, reproductive health services, and cardiac surgery, developing multi-sectoral RHD awareness programmes, understanding RHD pathogenesis and fostering international partnership for resource mobilization. There were volumes of peer reviewed publications focusing on the key priorities to fight RHD in different parts to Africa; both individually as well as through international collaborations. This article analyzed findings and reports from 1961 to 2018 on efforts to eradicate RF and RHD in Africa.